Streamlining the Synthesis of Pyridones through Oxidative Amination of Cyclopentenones.

Herein we report the development of an oxidative amination process for the streamlined synthesis of pyridones from cyclopentenones. Cyclopentenone building blocks can undergo in situ silyl enol ether formation, followed by the introduction of a nitrogen atom into the carbon skeleton with successive aromatisation to yield pyridones. The reaction sequence is operationally simple, rapid, and carried out in one pot. The reaction proceeds under mild conditions, exhibits broad functional group tolerance, complete regioselectivity, and is well scalable. The developed method provides facile access to the synthesis of 15N-labelled targets, industrially relevant pyridone products and their derivatives in a fast and efficient way.

Direct Access to Quinazolines and Pyrimidines from Unprotected Indoles and Pyrroles through Nitrogen Atom Insertion.

Recent advances in single-atom insertion reactions have opened up new synthetic approaches for molecular diversification. Developing innovative strategies to directly transform biologically relevant molecules, without any prefunctionalization, is key to further expanding the scope and utility of such transformations. Herein, the direct access to quinazolines and pyrimidines from the corresponding unprotected 1H-indoles and 1H-pyrroles is reported, relying on the implementation of lithium bis(trimethylsilyl)amide (LiHMDS) as a novel nitrogen atom source in combination with commercially available hypervalent iodine reagents. Further application of this strategy in late-stage settings demonstrates its potential in lead structure diversification campaigns.

Nitrogen atom insertion into indenes to access isoquinolines.

We report a convenient protocol for a nitrogen atom insertion into indenes to afford isoquinolines. The reaction uses a combination of commercially available phenyliodine(iii) diacetate (PIDA) and ammonium carbamate as the nitrogen source to furnish a wide range of isoquinolines. Various substitution patterns and commonly used functional groups are well tolerated. The operational simplicity renders this protocol broadly applicable and has been successfully extended towards the direct interconversion of cyclopentadienes into the corresponding pyridines. Furthermore, this strategy enables the facile synthesis of 15N labelled isoquinolines, using 15NH4Cl as a commercial 15N source.